title: Post-translational modifications guard yeast from misaspartylation.
abstract: Yeast aspartyl-tRNA synthetase (AspRS) is downregulated at the post-transcriptional level. This complex retro-inhibition mechanism causes the cell to equilibrate cellular concentrations of tRNAAsp, AspRS, and its encoding mRNA. This strategy hinders AspRS accumulation to keep misacylation of heterologous tRNAs under control. Here, the AspRS concentration was increased artificially in vivo but did not generate tRNAAsn and/or tRNAGlu misaspartylation or the logical consecutive post-translational stress. This work allowed the detection of an additional subtle cellular lock capable of blocking AspRS toxicity. This study revealed the presence of post-translational modifications in the N-terminal extension of AspRS. We hypothesize that by neutralizing the lysine-rich motif contained in this domain, the cell mobilizes an additional strategy that considerably reduces the probability of the enzyme binding and aspartylating noncognate tRNAs and thus harming its own translation.
authors.affiliation: ISIS-ULP, Laboratoire de Biologie Chimique, Strasbourg, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Ryckelynck
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Paulus
authors.forename: Magali
authors.initials: M
authors.lastname: Frugier
mesh_terms: D000595:Amino Acid Sequence; D049148:Aminoacylation; D001226:Aspartate-tRNA Ligase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D001224:Aspartic Acid / Q000378:metabolism*; D001710:Biotin / Q000378:metabolism; D015870:Gene Expression; D005839:Gentamicins / Q000494:pharmacology; D006031:Glycosylation; D008239:Lysine / Q000378:metabolism; D013058:Mass Spectrometry; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D020543:Proteome; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D005839:Gentamicins; D020543:Proteome; D001224:Aspartic Acid; D001710:Biotin; C010680:antibiotic G 418; D001226:Aspartate-tRNA Ligase; D008239:Lysine